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M Ota

Publications and source records attributed to M Ota.

At least 73 records · Page 4Linked to original sources
PubMed2000

HLA-DQB1*0601 is primarily associated with the susceptibility to cardiac sarcoidosis.

Cardiac sarcoidosis occurs in 1-5% of sarcoidosis patients. We previously reported a significant increase of the uncommon TNFA (tumor necrosis factor alpha) allele, TNFA2 with cardiac sarcoidosis in Japanese. In order to precisely localize the susceptible locus for cardiac sarcoidosis within the HLA region, genetic polymorphisms of classical HLA genes, non-classical HLA class II genes such as HLA-DMA and -DMB genes and several genes involved in the class I-mediated antigen presentation pathway (TAP1, TAP2, LMP2 and LMP7) were investigated. Further, association analyses using four polymorphic microsatellite markers located around the TAP1 and TNFA genes were also carried out. As a result, HLA-DQB1*0601 was found to be the most significantly associated allele, being more significantly increased than TNFA2. No significant increase of the DR52-associated DRB1 alleles (DRB1*03, 05, 06 and 08), which was suggested to be primarily associated with lung sarcoidosis, was observed in cardiac sarcoidosis. A primary role of DQB1*0601 in determination of the susceptibility to cardiac sarcoidosis was supported by association analysis using four polymorphic microsatellite markers, in which only the TAP1 microsatellite locus, the nearest marker to the DQB1 gene among the microsatellites tested, displayed a significant positive association with cardiac sarcoidosis. On the other hand, the HLA-DQB1*0501-DQA1*0101-DRB1*0101-B7 haplotype showed a negative association with the disease, as similarly observed in lung sarcoidosis. Thus, molecular mechanism for controlling the development of the disease related to HLA molecules are different between cardiac and lung sarcoidosis, whereas those for conferring a resistant trait may be similar to each other.

Alleles↗
PubMed2000

On the MICA deleted-MICB null, HLA-B*4801 haplotype.

A 100-kb deletion including the MICA gene was recently reported in the HLA-B48 (B*4801)-associated haplotype in Japanese. Interestingly, this MICA deletion is accompanied by a MICB null allele, MICB0107N. In order to further investigate the universality of the apparent tight linkage between these two events, we present data on high-resolution deletion mapping of eight HLA-B48-homozygous individuals. Among these, five carried the MICA deletion linked to MICB0107N, as originally reported. Conversely, the remaining three possessed an intact MICA gene of MICA008 or MICA010 allelic variant associated this time with a putative expressed MICB allele, MICB0102. These results may imply that the expression of both MICA and MICB molecules is indispensable to viability through a yet-to-be understood mutual interaction in immune surveillance.

Alleles↗
PubMed2000

Allele frequencies and haplotypic associations defined by allelic DNA typing at HLA class I and class II loci in the Japanese population.

HLA class I and class II allelic genotypes were determined in 371 unrelated individuals and 309 members of 81 families inhabiting the central Japan area. A total of 20 HLA-A alleles, 16 HLA-Cw alleles, 38 HLA-B alleles, 27 HLA-DRB1 alleles, 15 HLA-DQB1 alleles and 12 HLA-DPB1 alleles were detected. By the two-, three-, four-, five- and six-locus allelic association analyses extracted from the HLA-A to -DPB1 locus, 26 HLA-Cw-B haplotypes, 25 HLA-DRB1-DQB1 haplotypes, 42 HLA-Cw-B-DRB1 haplotypes, 37 HLA-Cw-B-DRB1-DQB1 haplotypes, 29 HLA-A-Cw-B-DRB1-DQB1 haplotypes and 21 HLA-A-Cw-B-DRB1-DQB1-DPB1 haplotypes with the frequencies of higher than 0.005 were recognized. Among 19 HLA-B alleles with the high allele frequencies (above 0.007), 9 HLA-B alleles, B*0702, B*1301, B*3701, B*3901, B*4006, B*4403, B*5201, B*5901 and B*6701 were found to be tightly associated with single HLA-Cw alleles. Most of HLA-DRB1 alleles showed strong associations with single HLA-DQB1 alleles, but DRB1*0802 and DRB1*1401 were associated with two different DQB1 alleles. Extended haplotypes carrying infrequent class I alleles with the allele frequencies of lower than 0.007 were defined by family studies. Gene frequencies and haplotypic associations within the entire HLA classical loci elucidated at the high resolution (four-digital) allelic level will provide useful information on anthropology, marrow donor registry, legal medicine and disease-association studies.

Family↗
PubMed2000

Analysis of T cell repertoire in the liver of patients with chronic hepatitis C.

Many T cells infiltrate into the liver of patients with chronic hepatitis C (CH-C). They are believed to play a crucial role in the immunopathogenesis of hepatic inflammation, but their clonality and specificity are unknown. The aim of this study was to clarify the characteristics of these T cells. We analysed the complementarity-determining region (CDR)3 size lengths of T cell receptor (TCR) beta-chains by size spectratyping, and determined the sequences of Vbeta CDR3 after subcloning Vbeta-specific polymerase chain reaction products. Spectratyping showed clonal expansions in all liver specimens, most of which showed more than two T cell clones. Moreover, many non-clonal T cells also accumulated in the liver. Clonality of the T cells suspected by spectratyping was confirmed by CDR3 sequencing. Although the sequences revealed no whole CDR3-shared clones among different patients, some common motif sequences were observed. Our data suggest that T cells are stimulated by several hepatitis C virus (HCV) epitopes, then accumulate in the liver of CH-C patients. Shared motifs of expanded T cell clones suggest that they might recognize the same regions of HCV peptides, but have differences due to HCV peptide mutational changes. These clones might also interact with non-clonal T cells and play a crucial role in the immunopathogenesis of CH-C.

Female↗
PubMed2000

A case of sporadic Creutzfeldt-Jakob disease with both plaque and synaptic-type deposition of prion protein.

We report a Japanese case of sporadic Creutzfeldt-Jakob disease (CJD) with particular clinical course and neuropathological findings. A 74-year-old female exhibited parkinsonism and later, dementia, myoclonus as well as visual hallucinations, lacking periodic synchronous discharges in the electroencephalogram. The duration of her illness was 2 years, longer than typical CJD cases which average 8 months' duration. Gray matter was severely affected, the Ammon's horn and subicular cortex were well preserved and many kuru plaques were observed in the cerebellum using routine histological stainings. Immunohistochemistry for prion protein (PrP) using both formic acid and hydrolytic autoclaving pretreatment revealed numerous prion plaques throughout the brain together with intense synaptic-type deposition of PrPCJD (abnormal isoform of PrP) in all gray matter examined, particularly in the Ammon's horn and subicular cortex. The definite combination of these two types of stain has never been reported previously in Japan other than in Gerstmann-Sträussler-Scheinker syndrome. Relative resistance of the Ammon's horn and subicular cortex to the PrPCJD deposition is also discussed.

Aged↗
PubMed2000

Effect of activated human protein C on disseminated intravascular coagulation induced by lipopolysaccharide in rats.

Protein C is the zymogen of an anticoagulant serine protease and is converted to its active form (activated protein C: APC) by thrombin in the presence of thrombomodulin. APC plays an important role in regulating coagulation and fibrinolysis by inactivating not only blood coagulation factors Va and VIIIa but also type-1 plasminogen activator inhibitor (PAI-1). The aim of the present study was to examine the effect of a human APC product (designated as CTC-111), compared with that of heparin, on the disseminated intravascular coagulation (DIC) induced by lipopolysaccharide (LPS) in rats. LPS (1 mg/kg/h) infusion was performed through a femoral vein for 4 h. One-fifth amount of the total dosage of CTC-111 or heparin was injected into the other femoral vein, followed by a 4-h infusion of the remainder. Both CTC-111 (10,000-100,000 U/kg) and heparin (400-800 IU/kg) inhibited the decrease in platelet count and fibrinogen level equally. The prolonged activated partial thromboplastin time and prothrombin time observed in DIC rats were further elongated in both CTC-111- and heparin-treated rats. But, this prolongation was less in CTC-111-treated rats than in the heparin-treated ones. Heparin inhibited the increase in fibrin and fibrinogen degradation products more prominently than CTC-111. On the other hand, CTC-111 strongly inhibited the increase in PAI-1 activity but heparin did not. These results suggest that CTC-111 may enhance fibrinolysis through its direct inhibitory effect on PAI-1. The parameters for liver or renal damage, i.e., plasma glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), creatinine (Cre) and blood urea nitrogen (BUN), were significantly increased by LPS infusion. Both CTC-111 (100,000 U/kg) and heparin (800 IU/kg) decreased the increase in GOT and GPT levels significantly, whereas neither affected the increase in Cre or BUN. From these results, the activation of the blood coagulation system might partially contribute to the progression of liver damage caused by LPS, and might be less involved in the progression of renal damage in this model. In conclusion, CTC-111 showed both anticoagulant and profibrinolytic activity in the LPS-induced DIC model without excessive prolongation of coagulation time. From these results, CTC-111 is expected to be a useful remedy for DIC without the risk of bleeding.

Animals↗
PubMed2000

Overexpression of vascular endothelial growth factor is responsible for the hematogenous recurrence of early-stage gastric carcinoma.

Vascular endothelial growth factor (VEGF) is crucial for angiogenesis in various malignant tumors. However, it is still unclear whether VEGF is responsible for hematogenous metastasis after the curative resection of gastric carcinoma. In the present study, we evaluated the relevance of VEGF expression to the hematogenous recurrence of stage 1 or 2 primary gastric adenocarcinoma. Among 530 patients, 11 (2.1%) had hematogenous recurrence. Clinicopathological variables were compared between these 11 patients (group R) and 88 patients without intramucosal carcinoma who survived for more than 5 years (group S). Microvessel density (MVD) was assessed immunohistochemically along with VEGF protein expression in all patients from group R and 21 randomly selected patients from group S. There were significant differences in age, tumor size and VEGF expression in tumor tissue between the groups. Positive staining for VEGF protein was observed in all patients of group R, of whom 6 had strongly positive staining. On the other hand, 11 out of 21 patients in group S had positive staining and it was weak in all cases. Both the positive and strongly positive rate were significantly higher in group R than those in group S. There was no significant difference in MVD between the 2 groups (17.7 +/- 11.09/field in group R vs. 14.8 +/- 10. 27/field in group S) and no significant correlation between VEGF expression, MVD and venous invasion, though a weak correlation between the intensity of VEGF staining and MVD was observed (negative staining 12.1 +/- 10.51; weakly positive 16.67 +/- 10.41; strongly positive 19.7 +/- 9.97). Our results suggest that overexpression of VEGF, and not MVD or venous invasion, plays an important role in the hematogenous recurrence of curatively resected gastric carcinoma.

Adult↗
PubMed2000

Basal meningoencephalocele, anomaly of optic disc and panhypopituitarism in association with moyamoya disease.

Basal meningoencephalocele is frequently associated with midfacial anomaly, optic disc anomaly, brain anomaly, cerebrospinal fluid rhinorrhea, chiasma syndrome, and endocrinologic disturbance. The combination of basal meningoencephalocele and moyamoya disease is extremely rare. A 29-year-old man had basal meningoencephalocele (transsphenoidal type), anomaly of the optic disc (morning glory syndrome), panhypopituitarism and moyamoya disease. The patient was treated by hormone replacement, but surgical intervention was not required. Basal meningoencephalocele and moyamoya disease are a possible combination of the diseases.

Adult↗
PubMed2000

Prognostic significance of blood pressure and heart rate variabilities: the Ohasama study.

To investigate the association between cardiovascular mortality and short-term variabilities in blood pressure and heart rate, we performed a long-term prospective study of ambulatory blood pressure monitoring in Ohasama, Japan, starting in 1987. We obtained ambulatory blood pressure and heart rate in 1542 subjects >/=40 years of age. Blood pressure and heart rate variabilities were estimated as a standard deviation measured every 30 minutes by ambulatory monitoring. There were 67 cardiovascular deaths during the follow-up period (mean=8.5 years). The Cox proportional hazards model, adjusted for possible confounding factors, demonstrated a significant increase in cardiovascular mortality, with an increase in daytime systolic ambulatory blood pressure variability. A similar trend was observed in daytime diastolic and nighttime ambulatory blood pressures. Cardiovascular mortality rate increased linearly, with a decrease in daytime heart rate variability. Subjects in whom the daytime systolic ambulatory blood pressure variability was larger than third quintile and the daytime heart rate variability was lower than the mean-SD were at extremely high risk of cardiovascular mortality. The blood pressure and heart rate variabilities obtained every 30 minutes by ambulatory blood pressure monitoring were independent predictors for cardiovascular mortality in the general population.

Aged↗
PubMed2000

Analysis of HLA antigens in Mycobacterium avium-intracellulare pulmonary infection.

Mycobacterium avium-intracellulare (MAI) pulmonary infection may occur in subjects with no preexisting lung disease and no known immunodeficiency, showing radiologically nodular bronchiectasis. There have remained some unresolved problems in the pathogenesis of the disorder, including the predominance in elderly women and the presence of not deteriorated or deteriorated disease. In the present study, we examined whether immunogenetic susceptibility is present in the disorder. We evaluated 64 cases of MAI disease and analyzed their short-term natural history by assessing symptoms, sputum bacteriology, and chest computed tomographic findings. The frequencies of human leukocyte antigen (HLA) alleles in patients were compared with those in 100 healthy Japanese control subjects. We assayed the HLA-A, -B, -C, -DR, and -DQ antigens serologically. Among 64 patients, 37 (35 females) did not show deterioration, whereas 27 (24 females) showed deterioration after an interval of 30 +/- 15 mo. There was no significant frequency of HLA-B and -C alleles in either group. In 37 not deteriorated patients, DR-6 was positive in 14 (37.8%) patients but in only 16 (16%) control subjects (p = 0.0061, odds ratio [OR] = 3.20). DQ-4 was positive in 10 (27.0%) patients but in only 10 (10%) control subjects (p = 0. 0122, OR = 3.33). In 27 deteriorated patients, HLA-A26 was positive in 14 (51.9%) patients but in only 21 (21.0%) control subjects (p = 0.0015, OR = 4.05). MAI pulmonary infection with nodular bronchiectasis shows two types of outcome, deteriorated and not deteriorated. The subjects with A-26 antigen might indicate the deterioration of MAI infection.

Aged↗
PubMed2000

Comparison of substrate specificities of transglutaminases using synthetic peptides as acyl donors.

Transglutaminase (TGase) is an enzyme that catalyzes acyl transfer reactions between primary amines and Gln residues in proteins or peptides. Substrate specificities of TGase, Ca2+-independent microbial transglutaminase (MTGase), and Ca2+-dependent tissue type transglutaminase from guinea pig liver (GTGase) and fish, Red sea bream (Pagrus major), liver (FTGase), for acyl donors were investigated using synthetic peptides containing Gln residues and Gln analogues with different lengths of side chain. MTGase dose not recognize the Gln analogues as a substrate and has strict substrate specificities toward L-Gln. Substrate peptides with a variety of sequences around the Gln residue, GXXQXXG (X=G, A, S, L, V, F, Y, R, N, E, L) were synthesized and used as acyl donors. As an acyl acceptor, the fluorescent reagent monodancyl cadaverine was used and the reactions analyzed with RP-HPLC. Substitution of the C-terminal of a Gln residue with a hydrophobic amino acid accelerated the reaction by GTGase and FTGase. N-terminal substitution of Gln residues had similar effects on the reaction by MTGase.

Amino Acid Substitution↗
PubMed2000

[The problem of a long-term follow up in patients with renal cell carcinoma].

PURPOSE: We investigated on a problem of long-term follow up in patients with renal cell carcinoma. PATIENTS AND METHODS: A total of 287 patients with renal cell carcinoma treated in Nara Medical University and affiliated facilities from January 1980 to December 1990 were examined. And we investigated the trend of explanation to patients including 287 patients from 1991 to 1995. RESULTS: Up to December 1995, there are 76 patients (26.5%) unable to be followed and 211 patients able to be followed. The former group patients were less declared cancer rather than the latter group patients. Of 76, 22 patients (28.9%) might misunderstand completely recovering from the cancer disease. For the recent 5 years, those patients who were declared cancer increased, and those patients who were explained benign disease decreased. CONCLUSION: These results suggested that declaration of cancer is important for patients with renal cell carcinoma to be followed for a long-term.

Aged↗
PubMed2000

Comparison of in vitro cytotoxicity of N-acetyl and N-propionyl derivatives of phenolic thioether amines in melanoma and neuroblastoma cells and the relationship to tyrosinase and tyrosine hydroxylase enzyme activity.

Our laboratory has synthesized two new phenolic thioether amines, N-propionyl-4-S-cysteaminylphenol (N-Pr-4-S-CAP) and N[2-[(4-propionyloxyphenyl)thio]ethyl] propionamide (N,O-diPr-4-S-CAP). These compounds, along with the previously described phenolic thioether amine N-acetyl-4-S-cysteaminylphenol (N-Ac-4-S-CAP) and its acetyl form (N,O-diAc-4-S-CAP), are tyrosine-amine derivative analogues. The cytotoxicity of these compounds is thought to be tyrosinase dependent, which may make them suitable for targeted anti-melanoma therapy since only melanocytes and their malignant counterparts contain this active enzyme. To further investigate this hypothesis, we performed MTT [3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide] assays to determine the cytotoxicity of these compounds in 10 different cell lines. Specifically, we examined to what extent cytotoxicity is related to tyrosinase and tyrosine hydroxylase activity using melanoma and neuroblastoma cells, which have a common metabolic pathway using tyrosinase and tyrosine hydroxylase, respectively. The most sensitive cell line was the highly pigmented SK-MEL-23 melanoma cell line, which shows a very high tyrosinase activity with the highest melanin pigmentation. KAN and SK-NSH (two neuroblastoma cell lines), which have no tyrosinase activity but high tyrosine hydroxylase, were also sensitive. However, C32 (a non-pigmented melanoma with a lower tyrosinase activity) was also sensitive, and MeWo (a moderately pigmented melanoma with a high tyrosinase activity) was less sensitive. This in vitro study may indicate that there is a non-tyrosinase-mediated mechanism of cytotoxicity for phenolic thioether amines in addition to the tyrosinase-mediated one described previously.

Amides↗
PubMed2000

[Sitting position in the neurosurgery: the results of a questionnaire sent to neurosurgeons of medical colleges].

We analyzed questionnaire on the sitting position among neurosurgeons. We sent questionnaire to 80 medical colleges in Japan and obtained response from 61 universities (76.3%). The sitting position surgery was performed in 7 institutions (11.5%) and was not in other 54 (88.5%). The first reason for not adopting the sitting position was "other position was good enough to perform the surgery" (44 institutions, 81%). This reason exceeded "objection from the anesthesiologist" (17 institutions, 31%). Twenty institutions (33%) adopted or wished to perform the surgery in sitting position, indicating that neurosurgeons still are interest in performing the sitting position surgery. But 6 institutions adopting the sitting position predicted that the sitting position would diminish in the future, and the sitting position surgery would decrease in number in Japan.

Humans↗
PubMed2000

Localization of the pathogenic gene of Behçet's disease by microsatellite analysis of three different populations.

PURPOSE: Behçet's disease (BD) is known to be associated with HLA-B51 in many ethnic groups. However, the pathogenic gene responsible for BD is as yet unknown. To localize the critical region of the pathogenic gene, microsatellite markers distributed around the HLA-B gene were investigated. The BD patients studied were of three ethnic origins: Japanese, Greek, or Italian. METHODS: The total group consisted of 172 BD patients, of whom were 95 Japanese, 55 Greek, and 22 Italian. Eight polymorphic microsatellite markers distributed within 1100 kb of the HLA-B gene were analyzed using PCR and subsequent automated fragment detection by fluorescent-based technology. RESULTS: Among the eight markers, allele 348 of the MIB microsatellite was remarkably common in all three BD populations (Japanese, PC: = 0.000014; Greek, PC: = 0. 00047; Italian, PC: = 0.11). However, HLA-B51 was found to be the marker most strongly associated with BD in each population (Japanese, PC: = 0.000000000017; Greek, PC: = 0.00000032; Italian, PC: = 0. 0074). In genotypic differentiation between the patients and controls, only HLA-B51 was found to be significantly associated with BD in all three populations. Stratification analysis suggested that significant associations of BD with MICA and other microsatellites resulted from a linkage disequilibrium with HLA-B51. CONCLUSIONS: These results suggest that the pathogenic gene of BD is HLA-B51 itself and not other genes located in the vicinity of HLA-B.

Behcet Syndrome↗
PubMed1999

Strong hydrophobic nature of cysteine residues in proteins.

The differences between disulfide-bonding cystine (Cys_SS) and free cysteine (Cys_SH) residues were examined by analyzing the statistical distribution of both types of residue in proteins of known structure. Surprisingly, Cys_SH residues display stronger hydrophobicity than Cys_SS residues. A detailed survey of atoms which come into contact with the sulfhydryl group (sulfur atom) of Cys_SH revealed those atoms are essentially the same in number and variety as those of the methyl group of isoleucine, but are quite different to those of the hydroxyl group of serine. Moreover, the relationships among amino acids were also determined using the 3D-profile table of known protein structures. Cys_SH was located in the hydrophobic cluster, along with residues such as Met, Trp and Tyr, and was clearly separated from Ser and Thr in the polar cluster. These results imply that free cysteines behave as strongly hydrophobic, and not hydrophilic, residues in proteins.

Algorithms↗
PubMed1999

Design and synthesis of a globin fold.

We propose a simple method to find an amino acid sequence that is foldable into a globular protein with a desired structure based on a knowledge-based 3D-1D compatibility function. An asymmetric alpha-helical single-domain structure of sperm whale myoglobin consisting of 153 amino acid residues was chosen for the design target. The optimal sequence to fit the main-chain framework has been searched by recursive generation of the protein 3D profile. The heme-binding site was designed by fixing His64 and His93 at the distal and proximal positions, respectively, and by penalizing residues that protrude into the space with a repulsive function. The apparent bumps among side chains in the computer model of the converged, self-consistent sequence were removed by replacing some of the bumping residues with smaller ones according to the final 3D profile. The finally obtained sequence shares 26% of sequence with the natural myoglobin. The designed globin-1 (DG1) with the artificial sequence was obtained by expression of the synthetic gene in Escherichia coli. Analyses using size-exclusion chromatography, circular dichroism spectroscopy, and solution X-ray scattering showed that DG1 folds into a monomeric, compact, highly helical, and globular form with an overall molecular shape similar to the target structure in an aqueous solution. Furthermore, it binds a single heme per protein molecule, which exhibited well-defined spectroscopic properties. The radius of gyration of DG1 was determined to be 20.6 A, slightly larger than that of natural apoMb, and decreased to 19.5 A upon heme binding based on X-ray scattering analysis. However, the heme-bound DG1 did not stably bind molecular oxygen as natural globins do, possibly due to high conformational diversity of side-chain structures observed in the NMR and denaturation experiments. These results give insight into the relationship between the sequence selection and the structural uniqueness of natural proteins to achieve biological functions.

Amino Acid Sequence↗